tbuckley/cabot-search huggingface dataset:
Microbiome, socioeconomic status (SES), fiber intake, and response to checkpoint inhibitor therapy in patients with non-small cell lung cancer (NSCLC): A pilot study.
Authors: Monaliben Patel, Gurkan Bebek, Brandon Vu, Mahmoud Ghannoum, Nathan A. Berger, Debora S. Bruno
Journal: Journal of Clinical Oncology (2023)

e14710 Background: Lung cancer affects a disproportional number of socioeconomically disadvantaged patients (pts). Responses to checkpoint inhibitor therapy (CIT) vary. Microbiome diversity may correlate with benefit from CIT. High fiber diets lead to microbiome diversity. We hypothesize that unexplained lung cancer disparities may be in part due to differences in microbiome diversity determined by unhealthy dietary patterns dictated by lower SES. Methods: Following IRB review, 25 pts with metastatic NSCLC starting CIT-based treatment were enrolled. Pre-treatment oral and fecal samples were collected. 24-hour dietary recalls were obtained. SES index was calculated based on education, employment, housing and annual income. High fiber intake was defined as &gt; 20 g/day. Best treatment response per RECIST 1.1 was assessed. Microbial 16s rRNA were sequenced with Illumina MiSeq platform. Sequence analyses utilized QIIME 2 with DADA2 plugin. Taxonomic assignments used the Greengenes database. Microbiome composition was analyzed by calculating alpha diversity (Chao1, Shannon diversity and Simpson index), beta diversity and differential abundance of microbial compositions. Hierarchical linear model was constructed for each SES variable with and without biological covariates. Results: Pts with samples &gt;1000 operational taxonomic unit (OTU) levels were included (N = 22) in the analysis. 50% were male, median age was 71, 36% (8/22) were of Black race and 23% (5/22) were of low SES. Median fiber intake was 11.9 grams. Males had higher alpha diversity than females (p=.038). Pts with high fiber intake had greater fecal Proteobacteria compared to low fiber intake pts (p&lt;0.05). Bacteroides and Firmicutes fecal levels were significantly different for all pts compared to Human Microbiome Project (HMP) reported normal levels (p&lt;0.01). Actinobacteria and Proteobacteria levels for low-fiber intake pts were also significantly elevated compared to HMP normal levels (p&lt;0.05). There were no differences observed in microbiome when comparing SES index. However, high SES index patients had elevated fecal levels of Actinobacteria, Firmicutes and Proteobacteria and lower levels of Bacteroides compared to HMP levels. There was a trend towards higher alpha diversity of oral samples in partial responders pts compared to those with stable or progression of the disease (p=0.08). Conclusions: Pts with metastatic NSCLC exhibited different microbial composition compared to HMP normal levels. Associations between SES and microbial distribution in such pts warrant further investigation. Increased sample size is needed to better determine differences in oral microbiome in responders to immunotherapy and better evaluate the role of sex in this setting.
Clinical utility of a novel non-invasive technology for monitoring severe neutropenia in anticancer therapy.
Authors: Manuel Alva Bianchi, Toshiaki Iwase, Pablo Tolosa Ortega, Pablo Justo Jiménez, Antonia Rodriguez Izquierdo, Tycho Baumann, Ana Jiménez Ubieto, Rodrigo Sanchez-Bayona, Elizabeth Pottier, Anthony Shelton, José Manuel Pérez-García, Juan Jose Garcia-Mosquera, Alejandro Martinez-Bueno, Ephraim P. Hochberg, Andrea Martinez, Cesar Nunez, David McCall, Naoto T. Ueno, Eva M Ciruelos, Branko Cuglievan
Journal: Journal of Clinical Oncology (2023)

e13632 Background: Every year more than 140,000 patients receiving anticancer therapy for malignancies in the US experience febrile neutropenia. Early detection of severe neutropenia could enable preventive strategies to reduce the incidence of febrile episodes. PointCheck is a novel portable optical device that can noninvasively monitor for severe neutropenia at home using microscopy and artificial intelligence. Preliminary clinical results of this device including usability (Lamaj et al., 2022), and sensitivity, and specificity (Pablo-Trinidad et al., 2019) for detection of severe neutropenia have already been reported. Here, we describe an exploratory clinical utility subanalysis. Methods: We conducted an international multicenter study with a primary endpoint of usability including mainly patients with hematological or breast cancer receiving therapy with intermediate/high risk for severe neutropenia, tested at two time points (baseline and nadir tests). Data included demographic information, cancer type, and a differential cell count within 120 minutes of the optical testing. The treating physician also completed an exploratory survey with 11 questions about the device´s potential clinical utility. A mixed-methods approach (descriptive statistics &amp; “Likert” analyses with R 4.2.2) was used to evaluate the results. Results: 79 patients were included in this exploratory subanalysis. The median age was 49.5 (IQR 10.5-78.5) years, and 64 (81%) patients were female. The most common diagnoses were breast cancer (63%) and lymphoma (20%). Preliminary utility results were favorable with attending physicians agreeing that PointCheck could have helped evaluate 85% of the patients. In 82% of the patients, physicians felt that the device could avoid preparation of chemotherapy infusions in the setting of neutropenia. In 73% of the patients, physicians would consider administration of G-CSF or prophylactic antibiotics when sustained grade IV neutropenia was detected. Conclusions: This novel technology is able to non-invasively monitor for severe neutropenia and can add clinical utility as assessed by treating oncologists. Further studies are needed to validate these results.
CancerX: A national public-private partnership to boost innovation in the fight against cancer.
Authors: Jennifer C Goldsack, Stephen Konya, Catharine Young, Edmondo J Robinson, Santosh Mohan
Journal: Journal of Clinical Oncology (2023)

e13637 Background: In early 2022, President Biden reignited the Cancer Moonshot, setting new national goals to cut the death rate from cancer by at least 50% over the next 25 years and improve the experience of people and their families living with and surviving cancer. In its first year, the reignited Cancer Moonshot announced over 25 new programs, policies, and resources in pursuit of these goals. In February 2023, to mark the one-year anniversary of the new national goals, the Cancer Cabinet – the expert and interagency body responsible for setting the Cancer Moonshot agenda across government agencies – announced three new actions, including the launch of CancerX - a public-private partnership (PPP) to act as a national accelerator to boost innovation in the fight against cancer. Methods: Leveraging foundational work of Moffitt Cancer Center, the U.S. Department of Health and Human Services (HHS), the Digital Medicine Society (DiMe), and Moffitt Cancer Center have come together to establish and lead CancerX as an open, collaborative public private partnership effort to rapidly accelerate the pace of cancer innovation in the US. This builds on momentum of prior successful multi-stakeholder collaborations led by these founders to advance digital innovation to reduce the incidence and burden of cancer for all people. This multi-stakeholder success will characterize CancerX, with additional organizations driving innovation in the fight against cancer participating across initiatives. Results: To speed the development and optimize the impact of innovative solutions across the continuum of cancer care – including prevention, detection, treatment, and transitions in care – CancerX is comprised of three key initiatives: 1) Pre-competitive evidence generation: a rolling series of multi-stakeholder efforts will develop evidence, best practices, toolkits, and value models to drive the success of the mission. 2) Accelerator: This program will provide mentorship, education, and exposure to funding and clinical partnership opportunities to a start-up cohort aligned with the mission. 3) Demonstration projects: These implementation projects will pilot novel, mission-aligned approaches to demonstrate their value and sustainability for scale to drive broad adoption. Conclusions: CancerX provides a structure for organizations whose missions are aligned with the Cancer Moonshot goals to rapidly advance innovative solutions for success at scale. Through a multi-pronged approach focused on 1) commoditizing best practices and aligning incentives, 2) coordinating access to research, mentorship, resources, and other collaborative opportunities, and 3) demonstrating success in practice to drive broad adoption, this PPP will reduce the incidence and burden of cancer for all people.
Continuous temperature monitoring: A systematic review of literature findings.
Authors: Ruth Anne Phillips, Sarah K. Bradley, Janvi Jani
Journal: Journal of Clinical Oncology (2023)

e13625 Background: Recent studies have determined continuous temperature monitoring (CTM) identifies fever up to 12 hours earlier than intermittent temperature monitoring in patients with neutropenic fever. In 2010, Van Vliet showed CTM enabled the early administration of antibiotics. Verma and colleagues (2021) reported that self-monitored temperature taking was frequently inaccurate. Nessle et al. (2022) observed 2 instances of fever, associated with bloodstream infections, detected by CTM 5 hours and 12 hours earlier than oral temperature. CTM records 8,640 data points in 24 hours versus the current standard of care (SOC), which typically measures up to 6 data points in 24 hours. The increased frequency of data collection presents a comprehensive picture of the patient’s status which enables earlier detection in trends or patterns of fever. As a result, earlier medical evaluation and prompt administration of antibiotics has led to improved patient care and outcomes. Methods: A literature review was executed to determine the validity of evidence available related to CTM utilization in both oncology and other high-risk therapeutic areas. Levels of evidence were assigned based on the design, methodology, validity, and applicability of the studies. Journal impact scores were added to support findings and implementation into real-world practices. A table was created to organize the data, including level of evidence, journal impact score, and study results. Results: This review of the literature included 17 documents related to CTM. Levels of evidence for CTM include 4 documents with Level 1 and 5 documents with Level 2 evidence. The journal impact scores found 6 of the 17 documents to be above 5. Overall, the study results showed a positive correlation between the use of CTM and earlier fever detection. Conclusions: CTM use has grown in recent years; however, there is still a need for randomized controlled trials to observe health economic, and clinical outcomes. CTM allows for earlier detection of fever, improving patient outcomes over SOC in high-risk patients. CTM should be considered a clinical decision tool to enhance current vital sign monitoring, thereby improving neutropenic patient care.
Phase I solid tumor trials (PHIstt) in the era of precision oncology (PO): A systematic survey.
Authors: Shannon Stockton, G. Dan Ayers, Cody L. Lee, Heather E. Laferriere, Jordan Berlin, Satya (Nanu) Das
Journal: Journal of Clinical Oncology (2023)

e13603 Background: In the era of PO, systemic therapies for patients (pts) with solid tumors have fundamentally changed from chemotherapy (CT) to targeted therapy (TT) and immunotherapy (IO). No study to the best of our knowledge has described PHIstt in this era. In this systematic survey, we describe the evolving features of PHIstt which began enrollment between 2010-2020, focusing on type of dose escalation scheme (DES) utilized, use of expansion cohorts (ECs) and nature of adverse events (AEs). Methods: The primary aim was to estimate the proportion of PHIstt which used rule-based DES. A literature search was performed by a biomedical librarian to identify PHIstt in adult patients published between January 1, 2000 – December 31, 2020 from a selection of 12 journals that publish PHIstt. However, we included studies enrolling between 2010-2020 to better capture agents in the PO era. We included trials with both single and multiple agents, and single and multiple modalities if the systemic therapy tested was being escalated. We excluded studies which only included intra-tumoral therapy, radiation therapy, or supportive care. Two reviewers assessed studies for inclusion and performed data abstraction; a 3rd reviewer established concordance. Results: Of 10,744 studies retrieved, 10,195 were non-topical or began enrollment prior to 2010; 437 studies in pts aged ≥ 18 years with advanced solid tumors were included. A median of 31 pts were enrolled per study (IQR 19-50), with median age 60 years in escalation cohorts. In studies reporting pt sex, 45.7% were female, and 53.9% were male. The most common classes of therapeutics were TT (47.6%), IO (22%), and CT (6.9%). Only 40.1% of studies reported ECs in the primary paper, and 46.6% of ECs used genomic selection. Rule-based designs (which assign patients to dose levels based upon prespecified rules of actual AE observations) were used in 89% of PHIstt; a 3+3 DES was used in 80.5% of these studies. With regards to grade 3/4 AE reporting, 56.6% of studies reported treatment-related AEs, 21.3% reported treatment-emergent AEs and 10.7% did not specify how they were reported. The most common class of grade 3/4 AEs was hematologic (37.1%). The most common dose-limiting toxicity classes were other (64.6%) and gastrointestinal (16.9%). Of all the drugs tested in PHIstt, 37.5% were tested subsequently in phase II while 10.3% garnered licensure. Conclusions: There is room for improvement in the trial design of PHIstt which may lead to more regulatory success. Some areas we identified include the more regular adoption of genomically selected ECs, more consistent reporting of AEs and diversification beyond rule-based designs to better assess safety/efficacy profiles of non-CT agents. Dose-Escalation Designs. [Table: see text]
Relationship between ICOS and ICOS ligand RNA expression patterns with tumor type, tumor mutational burden, and clinically relevant immune checkpoints.
Authors: Mina Nikanjam, Shumei Kato, Daisuke Nishizaki, Donald A. Barkauskas, Sarabjot Pabla, Mary K. Nesline, Jeffrey M. Conroy, Aung Naing, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2023)

e14669 Background: ICOS (inducible T-cell co-stimulator) has a unique ligand (ICOSL). Together they contribute to both antitumor responses/immune stimulation and potentiating immunosuppression. The interaction of ICOS and ICOSL can stimulate CD4 and CD8 ICOS-positive T-cell populations, but also can increase immunosuppressive regulator T-cells. ICOS agonists and antagonists are both under development as novel therapies. We aimed to quantify ICOS and ICOSL expression relationships with tumor type and other clinically relevant checkpoint inhibitors along with evaluating relationships between ICOS and ICOSL expression patterns. Methods: Data from 514 patients with advanced solid tumors at the University of California San Diego were used in the analysis. RNA expression levels of ICOS, ICOS ligand, PD-1, PD-L1, LAG-3, and CTLA-4 from tumor specimens were analyzed at OmniSeq. Tumor mutational burden (TMB) was also evaluated. Univariate analyses (Fischer’s exact tests) and multivariate analysis (logistic regression) were conducted in SAS v 9.4 to determine relationships between high (&gt;=75 percentile RNA rank) and low (0-24 percentile RNA rank) ICOS and ICOSL expression with age, gender, cancer type, high LAG-3, high TMB, high CTLA4, high PD-1, and high PD-L1. The relationship between ICOS and ICOSL high or low expression were also assessed. Results: Seventy patients had high ICOS (14%) and 192 had high ICOSL (37%) while low ICOS was seen in 226 (44%) and low ICOSL was seen in 76 (15%). High ICOS RNA levels were independently associated with patients not having colorectal cancer (p=0.0009), tumors with high PD-1 expression (p=0.025), tumors with high PD-L1 expression (p&lt;0.0001), and tumors with high CTLA-4 expression (p&lt;0.0001). Low ICOS RNA levels were independently associated with patients whose tumors did not have high PD-1 (p=0.0006), tumors that did not have high PD-L1 (p=0.01), tumors that did not have high CTLA-4 expression (p&lt;0.0001), and those with low ICOSL expression (p=0.0007). High ICOSL was independently associated with a diagnosis of colorectal cancer (p=0.0015), tumors that did not have high PD-L1 expression (p=0.003), and tumors with high CTLA4 (p=0.0001). Low ICOSL was independently associated with patients who did not have colorectal cancer (p=0.0001) and tumors with low ICOS expression (p=0.0032). Conclusions: ICOS and ICOSL RNA expression patterns can provide insight into the complicated ICOS/ICOSL immune checkpoint signaling pathway and help support rational immunotherapy combinations as part of a precision medicine approach. Both stimulators and inhibitors of the ICOS/ICOSL axis are being developed, and their proper application may require interrogation of the individual patient’s tumor/environment.
Management of immune related adverse events through electronic multidisciplinary consultation: Five years of experience from Peking Union Medical College Hospital.
Authors: Xiaoyan Liu, Yuequan Shi, Dongming Zhang, Minjiang Chen, Yan Xu, Jing Zhao, Wei Zhong, Mengzhao Wang
Journal: Journal of Clinical Oncology (2023)

e14712 Background: The increasing occurrence of immune-related adverse events (irAEs) pose a growing challenge for patients receiving immunotherapy. We sought to evaluate the utility of telemedicine in improving access to the multidisciplinary service and to provide a comprehensive overview of practical issues in the diagnosis and management of irAEs. Methods: A virtual multidisciplinary service dedicated to the diagnosis and management of irAEs was launched in July 2018. Data were collected using a digital referral system. Results: Data were collected from 1 July 2018 to 30 June 2022. After excluding 11 consultations that were lost to follow-up or had incomplete medical records, 278 consultations were included in this study. 187 consultations related to the diagnosis and management of irAEs; 68 related to the management of irAEs; 23 related to the suitability of immunotherapy. The diagnosis of irAE was ruled out in 23% (43/187) of cases. The differential diagnosis included overlapping toxicity attributed to concurrent use of targeted therapy or chemotherapy (n = 16), comorbidities (n = 11), infection (n = 10), and cancer progression (n = 6). A diagnosis of irAE was confirmed in 206 cases. Of these, 131 cases were single organ/system irAEs and 75 cases were multiple organ/system irAEs. 83% of these were grade 3-4. The most common confirmed irAEs were interstitial lung disease (n = 45), diarrhoea/colitis (n = 41), liver dysfunction (n = 38) and myocarditis (n = 33). Initiation of corticosteroids was recommended in 100% (138/138) of treatment-naïve patients. The most commonly recommended corticosteroid dose was 1-4 mg/kg/d (n = 83, 45%). Corticosteroid dose adjustment was recommended in 90% (61/68) of treated patients, including dose escalation (n = 19), dose re-escalation or prolonged tapering (n = 30), and rapid tapering (n = 12). Cardiovascular, pulmonary, rheumatic and hepatic irAEs were the top four irAEs requiring immunosuppression in addition to corticosteroids. Intravenous immunoglobulin (n = 108), tocilizumab (n = 51), mycophenolate mofetil (n = 41), and infliximab (n = 21) were the four most commonly recommended immunosuppressants. Consultation recommendations were followed in 87% (166/191) of cases. Clinical improvement was observed in 83% (137/166) of cases. Conclusions: This study demonstrated the feasibility of the electronic multidisciplinary consultation in the diagnosis and management of irAEs. Common challenges in the diagnosis of irAEs were identified, mainly the differential diagnosis of non-immune toxicity, infection, cancer progression, or comorbidities. Awareness of differential diagnosis should also be raised in patients suspected of irAE flare. The use of corticosteroids and additional immunosuppressants needs to be further investigated.
A study to evaluate the safety, tolerability, and efficacy of IBI939 in combination with sintilimab in patients with previously untreated locally advanced unresectable or metastatic PD-L1–selected non–small-cell lung cancer (NSCLC): Updated efficacy and safety results.
Authors: Chunjiao Wu, Baogang Liu, Lin Wu, Tongmei Zhang, Ke Wang, Liyun Miao, Jingxun Wu, Huijuan Wang, Jian Fang, Xingya Li, Wei Zhang, Yanping Hu, Xiaodong Mei, Yong Song, Jing Zhu, Ying Xin, Yue He, Yuling Chen, Jiawei Ye, Ying Cheng
Journal: Journal of Clinical Oncology (2023)

e14578 Background: According to studies in patients (pts) with solid tumors, T-cell immunoreceptor with Ig and ITIM domains (TIGIT) plays an important role in tumor immunosurveillance. The preliminary results showed that IBI939 plus sintilimab demonstrated improved PFS benefit and manageable safety profile in PD-L1 TPS ≥ 50% NSCLC pts with no prior systemic treatment (Ying Cheng et al. ESMO-IO, 2022). Here we report updated efficacy and safety data of this study. Methods: Eligible pts with systemic treatment-naïve, advanced or metastatic NSCLC, PD-L1 TPS ≥ 50%, and driver gene negative were enrolled and randomized 2:1 to IBI939 20 mg/kg plus sintilimab 200 mg IV Q3W (arm A) or sintilimab 200 mg monotherapy IV Q3W (arm B). The primary objective was to evaluate the ORR per RECIST v1.1. The secondary objectives include evaluation of PFS per RECIST v1.1, OS, and safety. Results: Of 42 pts enrolled, 28 pts (median age: 65; adenocarcinoma: n=19; brain metastasis: n=7) and 14 pts (median age: 58; adenocarcinoma: n=6; brain metastasis: n=1) were in arm A and arm B, respectively. As of Jan 1 st , 2023, with a median PFS follow-up of 12.2 months (95% CI, 11.1-13.9) in arm A and 11.3 months (95% CI, 10.8-13.6) in arm B. The median PFS per investigator was 13.2 months (95% CI, 6.7-16.5) in arm A vs 6.4 months (95% CI, 1.4-NA) in arm B (HR: 0.62; 95% CI, 0.26-1.43). All 42 pts were included for safety analysis. The overall safety profile was consistent with the latest previous report, with no new safety signals identified in each arm. The incidence of TRAEs was 96.4% vs 78.6% (5 pts in arm A and 6 pts in arm B experienced ≥ grade 3 events), respectively. Grade ≥ 3 immune-related AEs (determined by the investigator) were reported in 3 (10.7%) pts in arm A and 4 (28.6%) pts in arm B. All reported irAEs were manageable. One pt in each arm experienced TEAE leading to end of treatment. There was no TEAE leading to death happened in arm A. Two pts experienced grade 5 TEAE in arm B, which was unknown cause of death and respiratory failure. Conclusions: With longer follow-up time, IBI939 plus sintilimab demonstrated durable PFS benefit and manageable safety profile in PD-L1 TPS ≥ 50% NSCLC patients with no prior systemic treatment. Clinical trial information: NCT04672369 .